MALARIA 2010

Historical Perspective

The word malaria is derived from the Italian words “Mal” and “aria” which mean “bad

air”. The name was due to the fact that malaria was thought to be caused by bad air from

marshes. It was later it was discovered that it was caused by a germ carried by an insect, the

Anopheles mosquito which spreads the illness by biting people.

The germ was discovered in the blood of malaria patients by Charles Alphonse Laveran,

a Frenchman, in 1880. Ronald Ross (1857 - 1932), an Englishman, who worked extensively in

India, finally solved the riddle. He noticed that people did not seem to catch malaria from each

other, and he suspected that the Anopheles carried the germ. To prove this, he made experiments

in the plains surrounding Rome, where Anopheles was common. Healthy people spent the day

among patients, and at night they retired to screen houses. None caught malaria. Then two men

in England allowed themselves to be bitten by Anopheles brought from the Roman plains, after

they had bitten malaria patients. The men developed malaria!!

Malaria has been known to be a serious acute and chronic relapsing infection in man

characterised by periodic paroxysms of chills and fever, anaemia, splenomegaly and often fatal

complications. Malaria also is found in apes, monkeys, rats, birds and reptiles. It is one of the

most ancient infections known to man. It was noted in some of the earliest records in the 5 th

century BC, when Hippocrates differentiated type of fever.

An effective treatment was known long before the cause was understood: the

therapeutically active bark of the Cinchona tree, and from 1700, its most active principle,

Quinine, was used universally for the treatment of malaria.

Aetiology

Malaria is caused by intracellular Plasmodium protozoa. Three factors are involved in the

transmission of malaria, namely, the parasite, the vector and the host. The parasite, a protozoan
(unicellular organism) is known by the generic name Plasmodium. Those affecting man are of

four different kinds distributed in various regions of the world. They can be identified in the

peripheral blood because of their specific shapes in the red blood cells (RBC). They are, in order

of dates of discovery Plasmodium malariae, P. vivax, P. ovale, and P. falciparum. Each variety

has two life cycles. One in the host (asexual phase) where the invasion of body organs

(particularly the liver) and RBC takes place and the other, in the vector (sexual phase) where the

sexual forms of the parasite combine to form a fertilised egg (see Life Cycle) in the stomach

cavity of the mosquito. After a series of further transformations, sporozoites enter the salivary

glands of the mosquito and are inoculated into a new host with the blood meal. P. vivax and P.

ovale are characterised by persistent tissue forms chiefly in the liver, from whence fresh attacks

of clinical malaria can arise even in the absence of re-infection. However, this mode of infection

is only of clinical significance in expatiates living in malaria endemic zones but who wish to

relocate back home in temperate countries. In such individuals, the persistent tissue forms can

cause fresh attacks of malaria even more than five years after leaving the malarious area.

EPIDEMIOLOGY

Malaria is a worldwide disease, and there are probably more cases of it than any other

infection. It is the leading communicable disease in most regions of the tropics and sub-tropics,

Nigeria inclusive. It is estimated that about 2 billion (about ⅓ of the world population) are

exposed to the risk of infection. More than 30% of all deaths in infants and children below the

age of three years can be ascribed to malaria. It is said to account, conservatively, for about a

million deaths in Africa every year. In our hospitals, about 60% of our patient attendance can be

attributed to malaria.

In our Children Emergency Room in the Wesley guild Hospital, Ilesa (a unit of the

Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife) about 1600 children are

admitted on emergency basis every year; about 50% of these are admitted because of severe
anaemia. More than 90% of these cases of severe anaemia can be attributed to malaria!!

Falciparum malaria is often the cause of the severe forms of malaria even though vivax and

falciparum malaria together represent 95% of all infections.

Vivax malaria is the most widespread variety, mainly because of its ability to withstand

therapy and remain chronic. Falciparum malaria has the most severe symptoms and is the most

frequently fatal; it requires higher temperatures for optimal development and it is confined more

closely to the tropics.

PATHOGENESIS

Fever, anaemia, immunopathologic events and tissue anoxia are four important

pathologic processes that have been identified with malaria. Fever occurs when erythrocytes

rupture and release merozoites and pyrogens.

Anaemia is caused by haemolysis, sequestration of erythrocytes in the organs

particularly, the spleen, and suppression of erythrocyte production in the one marrow.

Haemolysis is even more severe in a child with iron deficiency anaemia. More than 70% of the

children with severe anaemia in our unit tend to have blood film appearance suggestive of ion

deficiency.

Cytoadherence of infected erythrocyte to vascular endothelium occurs particularly in P.

falciparum malaria. This may lead to obstruction of the blood flow and capillary damage with

resultant vascular damage, vascular leakage of proteins and fluid, and oedema and tissue anoxia

in the brain (pathogenesis of cerebral malaria), heart, lungs, intestines and kidneys.

Immunopathologic events include polyclonal activation resulting in both

hypergammaglobulinaemia (as seen in Tropical splenomegaly syndrome or Hyper-immune

malaria syndrome) and formation of immune complexes. There is also immunosuppresion and

release of cytokines such as Tumour necrosis factor (TNF) that may be responsible for many of

the pathologic features of the disease.

IMMUNITY

Newborns and young infants seldom have malaria and when they do, the infection is

rarely severe because of natural protection from the following mechanisms:

a. Antibodies tend to pass from the mother via the placenta to the baby during pregnancy.

b. The protection is further reinforced by antibodies against malaria that pass to the baby via

breast milk.

c. The foetal haemoglobin that persists in young infants usually up the age of six month tends to

be relatively resistant to parasitisation particularly by P. falciparum.

d. The breast milk is also relatively poor in para-aminobenzoic acid (PABA); PABA is needed

in abundance for the growth of plasmodium.

e. Some of the drugs the mother take against malaria infection will also protect the baby via the

breast milk (using the rule of thumb, about 10% of the dose gets transferred).

f. The vector-avoidance behaviour of the mother also minimises the exposure of the baby to the

biting of the mosquitoes and consequently of the transfer of the sporozoites.

The infant begins to develop his own immunity as he grows older; however, the

immunity after plasmodium infection is incomplete. Subsequent severe disease may be averted

but complete eradication or prevention of future infections is not achieved. In some cases,

parasites circulate in small numbers for a long time, but depending on the level of immunity,

parasites may be prevented from rapidly multiplying and causing severe illness. Repeated

episodes of infection do occur because the parasites do develop a number of immunity-evasive

strategies such as:

i. Intracellular replication.

ii. Rapid antigenic variation.

iii. Alteration of the host immune response that includes partial immunosuppresion.
 Apart from haemoglobin F, possession of trait of sickle erythrocyte (carrier state) resists

malaria parasite growth because infected cells readily get deformed and they are cleared by the

spleen from circulation. Duffy-blood-group-antigen lacking erythrocytes are resistant to P. vivax.

Even though infants and young children try to develop their own immunity to malaria;

children between 6 months to 5 years have little specific immunity to malaria species and

therefore suffer yearly attacks that can even be fatal. As immunity is acquired, severe symptoms

of malaria become less common, this may not happen until the individual is about 11 years.

CLINICAL MANIFESTATION

Malaria is a great masquerade and it can mimic most febrile ailments. However, the

classic presentation after an average incubation period of 2 weeks [P. falciparum 9 –14 days, P.

vivax 12 – 17 days, P. ovale 16 – 18 days and P. malariae 18 – 40 days] includes febrile

paroxysms alternating with periods of fatigue but otherwise relatively well. Other symptoms

include high fever, particularly in children, rigors, sweats, headache, myalgia, abdominal and

back pains, nausea, vomiting, pallor and diarrhoea (in young children). Paroxysms coincide with

the rupture of schizonts and its occurrence depends on the specie of malaria. It occurs every 48

hours with P. vivax and P. ovale and every 72 hours with P. malariae. However, periodicity is

less apparent with P. falciparum especially in children where the fever may be continuous. In

infants the range of symptoms and signs may be myriad and non-specific; which may include

diarrhoea, vomiting, pallor, cyanosis, drowsiness, hepatomegaly, e.t.c.

P. falciparum is the most severe form and is associated with more intense parasitaemia

that can be up to 60% 0f RBC since both mature and immature RBC are parasitised. P. vivax and

P. ovale primarily infect immature RBC while P. malariae infect only mature RBC. While the

infections are usually mild in other forms of malaria, the fatality in the P. falciparum can be as

high as 30% if not urgently addressed.

 Rarely, there may be prenatal or perinatal acquired malaria. Congenital malaria is an

important cause of spontaneous abortion, miscarriage, stillbirth, and neonatal death, e.t.c. The

first sign or symptom of congenital malaria occurs usually at about 2 weeks (10 – 30 days) but

may occur as early as 14 hours. The signs and symptoms are no-specific; it may include fever,

restlessness, jaundice, poor feeding, cyanosis, hepatosplenomegaly, apnoea e.t.c.

DIAGNOSIS

The diagnosis is established by identification of the organisms on Giemsa-stained smears

of peripheral blood. Giemsa stain is said to be superior to either Wright’s or Leishman’s stain.

Both thick and thin blood smears should be examined. The thick blood film identifies the degree

of parasitisation while the thin film will identify the Plasmodium species causing the infection.

P. falciparum is most likely to be identified from blood just after a febrile paroxysm, but timing

the smears is less important than obtaining them several times a day. A single negative blood

smear finding does not exclude malaria. There may be a need to repeat the smears as frequent as

every 4 – 6 hours a day.

The newly introduced malaria rapid diagnostic tests hold great promise. These are

membrane-based immuno chromatographic tests which signify presence of specific malaria

antigens like Histidine rich protein-2 (HRP2) and Plasmodium Lactate dehydrogenase (PLHD)

by a colour change on a Nitrocellulose strip. They are rapid, simple and sensitive. They can be as

sensitive as the thick blood smear. Polymerase chain reaction testing which is even more

sensitive can also be used for diagnosis. However, all these are not generally available in the area

where malaria is endemic.

DIFFERENTIAL DIAGNOSIS

This is very broad; in fact any “fever” in the tropics is assumed to be malaria until proven

otherwise. This will include typhoid fever, yellow fever, tuberculosis, pneumonia, meningitis,

septicaemia, e.t.c. it also include viral ailments like influenza, hepatitis and even common cold.

The doctors in the tropics are aware of the ubiquitous nature of malaria to the extent that

it has been shown that more than 50% of patients clinically diagnosed with malaria have

illnesses attributable to some other causes.

TREATMENT

Aim

1. Uncomplicated malaria

a. The objective of treating uncomplicated malaria is to cure the infection.

b. A secondary but equally important objective of treatment is to prevent the emergence

and spread of resistance to anti-malarials.

2. Severe malaria

a. The primary objective of anti-malarial treatment in severe malaria is to prevent death.

b. Prevention of recrudescence and avoidance of minor adverse effects are secondary.

c. In treating cerebral malaria, prevention of neurological deficit is also an important

objective.

d. In the treatment of severe malaria in pregnancy, saving the life of the mother is the

primary objective.

Impact of resistance

Initially, at low levels of resistance and with a low prevalence of malaria, the impact of

resistance to anti-malarials is insidious. The initial symptoms of the infection resolve and the

patient appears to be better for some weeks. When symptoms recur, usually more than two
weeks later, anaemia may have worsened and there is a greater probability of carrying

gametocytes (which in turn carry the resistance genes) and transmitting malaria. However, the

patient and the treatment provider may interpret this as a newly acquired infection. At this stage,

unless clinical drug trials are conducted, resistance may go unrecognized. As resistance worsens

the interval between primary infection and recrudescence shortens, until eventually symptoms

fail to resolve following treatment. At this stage, malaria incidence may rise in low transmission

settings and mortality is likely to rise in all settings.

From time immemorial, Quinine, a derivative of cinchona bark has been the drug of

choice in treating malaria until the ascendancy of Chloroquine in the late “sixties”. However, by

“early” eighties” resistance to Chloroquine was being noticed, not only in Nigeria but all over the

world. Presently, the national policy on the treatment of malaria recommends the use of

Artemisinin Combination Therapy (ACT) for acute attack of malaria. It is well-known that

Artemisinin is a drug derived from a plant that has been in use against malaria in China for

centuries. Artemisinin and its derivatives (Artesunate, Artemether, Artemotil and

Dihydroartemisinin) produce rapid clearance of parasitaemia and rapid resolution of symptoms.

They reduce parasite numbers by a factor of approximately 10 000 in each asexual cycle, which

is more than other current anti-malarials (which reduce parasite numbers 100- to 1000-fold per

cycle). Artemisinin and its derivatives are eliminated rapidly. When given in combination with

rapidly eliminated compounds (Tetracyclines, Clindamycin), a 7-day course of treatment with an

Artemisinin compound is required; but when given in combination with slowly eliminated anti-

malarials, shorter courses of treatment (3 days) are effective. Various drugs that have been

combined with Artemisinin included, Amodiaquine, Co-trimoxazole, Lumifantrine, Fansidar®,

e.t.c. The Artemisinin compounds are active against all four species of malaria parasites that

infect humans and are generally well tolerated but significant adverse effect have been observed

(circa 1:3000) type 1 hypersensitivity reactions (manifested initially by urticaria). These drugs

however have the advantage from a public health perspective of reducing gametocyte carriage
and thus the transmissibility of malaria. This may contribute to malaria control in areas of low

endemicity. Quinine, intravenously administered at least during the initial stage, is the drug of

choice in cerebral malaria. However, we have just shown that combining quinine with artemisin

in treating cerebral malaria reduces the period of the hospital stay in the sufferers.

According to Rev. Father Adodo, an alternative medical practitioner, who wrote in his

book – Then healing Radiance of the Soul, “the types of plants growing in a particular place

often reflect the need or problem in that particular place. Shortly before any epidemic or disease,

the plant which has the antidote begins to sprout. For every sickness, disease or lack, there is

always a medicinal plant growing nearby. It is left for human beings to open nature’s book of

wisdom and learn to use them.”

There are many plants in our folklores that are effective in the treatment of malaria. Yet,

the educated elite rarely use them but prefer to promote imported drugs. These common plants

include mango leaves, bitter leaves, lemon grass, guava leaves and the bark of lime tree, e.t.c. we

have tried some of the local herbs for patients suffering from malaria and we have found them to

be as effective as imported drugs. Nigeria must endeavour to contribute to the world of

discoveries instead of joining the mere consumers and buyers of medical science. I believe we

can do it and we need to do it; the time for the herbal revolution is now. According to one Dr.

Abudu of Ghana, “The animals, birds, trees and other forms of life in West Africa do not depend

on what similar forms of life in Europe or elsewhere can do for them. Yet, they thrive very well

and probably better than those in these distant places”. So, why must our on be different?

The use of ACT, which is multidrug approach, is remarkably similar to the logic behind

the use of whole plants. In the case of cinchona, it is well established that quinine is not the only

anti malarial agent in the bark. There are at least four known anti malarial alkaloids – quinine,

quinidine, cinchomine, and cinchonidine. In vitro these four alkaloids show additive properties

when combined, and a combination of quinine, quinidine and cinchonine is dramatically more

effective than quinine alone against drug-resistant malaria in vitro. Thus, although these
alkaloids are likely to act by similar mechanisms, they are still more effective combined that in

isolation and thus cross-resistance may not be as big a problem.

COMPLICATIONS

Severe anaemia is the most common complication that we manage in our children

emergency room; accounting for about 50% of cases seen in that unit. Apart from pathogenesis

of anaemia as explained above; the iron deficiency anaemia that is commonly seen among our

infants tends to exacerbate the anaemia in children with malaria. The iron deficiency can either

be due to unsupervised deliveries that are usually associated with our births or the low iron in the

weaning diets of our infants.

The indiscriminate use of antipyretics particularly, Paracetamol, also tend to increase the

parasite clearing time, among patients with malaria. This tends to worsen the anaemia associated

with malaria.

Cerebral malaria is also a serious complication and it is associated with severe anaemia in

30% of the cases. Majority of the sufferers are older infants and early pre-school children. The

fatality rate is 10 – 30% but rarely causes long-term sequelae if it is treated appropriately. As

with other complications, cerebral malaria is more likely inpatients with a parasitaemia of > 5%.

The symptoms always include impaired level of consciousness which may range from

drowsiness to deep coma. There may also be seizures and other CNS malformations. Lumbar

puncture reveals increased pressure and cerebrospinal fluid protein level with minimal or no

pleocytosis and normal glucose level. Febrile convulsion is also a complication and sometimes

this may be an early manifestation of cerebral malaria.

Other complications of malaria include renal failure (this may result from deposition of

haemoglobin in renal tubules, decreased renal blood flow and acute tubular necrosis). Renal

failure may also result from complications of malaria known as “Black water fever” or when
patients with G6PD deficiency who have malaria are treated with Sulphonamide-containing anti-

malarial. Black water fever result when complement and antibodies directed against parasite-

laden erythrocytes produce severe haemolysis that may result in renal failure and the so-called

“Coca-Cola urine” production.

Pulmonary oedema, metabolic acidosis, thrombocytopaenia, splenic rupture,

hypoglycaemia, hyperparasitisation and algid malaria are known complications. Algid malaria is

a rare form of P. falciparum that occurs with over-whelming infection, hypotension,

hypothermia, weak pulses, shallow breathing, pallor and vascular collapse. Nephrotic syndrome

is also said to be a long-term complication of P. malariae infection.

PREVENTION

Sir Ronald Ross stated this explicitly more than 100 years ago that the right way to

prevent malaria was to destroy the breeding-places of the mosquito. This he said can be done, by

covering of stagnant water with paraffin to kill the larvae of the mosquitoes, and spraying huts,

houses and bushes with chemicals.

Apart from these well-recognised measures, there are some local control measures that

are known to help. Local chickens do feed on the larvae of the mosquitoes and keeping chickens

may help control the vectors. Brooms are also used to kill mosquitoes on the window sills where

they usually reside at night. Insecticide treated nets are now being touted as one of the “big

weapons” of the Roll Back Malaria (RBM) programme. Insecticide treated paints can also be

used to paint the rooms especially where children will be sleeping. The painting can be repeated

every 6 months. Some plants like lemon grass and basil leaves are known to have insect repellent

activity and they can be planted round the house.

In those countries where successful malaria eradication programmes have been carried

out, the infant mortality has fallen by a half to a third; Sri Lanka is the often-quoted example.
 As desirable as eradication of malaria is, the greatest obstacle is the attitude of the people

who often suffer from the ailment. They create the slums where the vectors thrive. The rapid

urban migration that is taking place in most of Africa, Nigeria inclusive, is not helping the

matter. Overpopulation, as it obtains in the slums of the cities, is a situation of having large

numbers of people with too few resource and too little space, is closely associated with poverty

and severe form of malaria.

The word malaria which means bad air was thought to be a misnomer but more recent

findings have shown that this may not strictly be so. Socks that were collected from different

people were hung overnight on piles in open air like fishing nets in water. Some of the

participants were people with sweaty and smelly feet. Others were people that may be described

as owners of normal, healthy feet. In the morning, socks from people with sweaty and smelly

feet had gathered many mosquitoes trapped in them, whereas, the other category of socks had

fewer or no mosquitoes in them. This has led to the conclusion that there is something in the

moist, smelly socks which attracts mosquitoes. This means that unkempt persons living in an

environment with poor drainage is more susceptible to mosquito bites and consequently, attacks

of malaria.

One’s eating habit can also be decisive in the extent to which one will be susceptible to

attack of malaria. One Professor Sali, interestingly an ENT surgeon from Uganda, believes that

Anopheles mosquitoes do not contact malaria fever despite all the plasmodia in the saliva and

blood because its own blood is full of Vitamin C and it converts practically everything it eats

into Vitamin C. It is conceivable that adequate intake of Vitamin C will minimise attack of

malaria particularly the severe forms. Vitamin C is available in fruits and vegetables particularly

the citrus fruits. Regular intake of lime fruits is a traditional lifestyle some Yoruba people adopt

to ensure god health.

The pH of the blood is towards the alkaline side (about 7.365). Dr. R.O. Young and his

wife believe that the body’s predisposition to infections and other ailments is due to an
imbalance between the acidity and alkalinity in the body. Unfortunately, most of the foods we

like to eat tend to create chronic over-acidity in our body. One old woman succinctly put it “Òta

enu ni ore ikun, ore ikun ni ota enu” i.e. what is agreeable to the palate tend to be injurious to the

body and vice versa. Most junk food are acidifying and it is those who are in the cities who

hardly have time to cook good food and they are likely to live mainly on refined diet with little

intake of vitamins and trace elements, which among other functions, are good antioxidants. Like

most other diseases, upbuild of free radicals in the body is likely to provide a fertile place for

proliferation of malaria parasites in the blood.

Most alkalinising nutrients are food in vegetables and some fruits. Fruits that alkalinise

are not usually sweat viz: lime, lemon and grapefruit. It is said that of the five flavours (bitter,

sweat, sour, salty and spicy); the bitter principle appears to offer terrific antidote to diseases.

Probably that is why the Yoruba of yore would sing: ‘A layombere, mo rie. Ki oto di ejo, Mo ti

di abere. Eje mi si koro bi ewuro’. Meaning, ‘Alligator, I see you. Before you become a snake, I

have become a needle. And, my blood is as bitter as bitter-leave’. Even in the Bible, Roman 14:

2; it is written “For one believes he may eat all things, but he who is weak eats only vegetables.”

I do not think one needs to be weak to incorporate lot of vegetables in one’s diet.

It is therefore not surprising that the Yoruba believe that the bitter-leave tree is the king

of all trees. Hence, one will advise that individuals who are unusually prone to severe attacks of

malaria (e.g. Hb SS) need to be taking lots of bitter-leaf soup and its decoction instead of

Proguanil and Pyrimethamine (malaria chemoprophylaxis) to which resistance readily develop.

GLOSSARY

1. Anti-malarial combination therapy. Anti-malarial combination therapy is the simultaneous

use of two or more blood schizontocidal drugs with independent modes of action and thus

unrelated biochemical targets in the parasite. The concept is based on the potential of two or
 more simultaneously administered schizontocidal drugs with independent modes of action to

improve therapeutic efficacy and also to delay the development of resistance to the individual

components of the combination.

2. Artemisinin-based combination therapy (ACT). A combination of Artemisinin or one if

its derivatives with an anti-malarial or anti-malarials of a different class.

3. Asexual cycle. The life-cycle of the malaria parasite in host red blood cells (intraerythrocytic

development) from merozoite invasion to schizont rupture (merozoite →ring stage

→trophozoite →schizont →merozoites). Duration approximately 48 h in Plasmodium

falciparum, P. ovale and P. vivax; 72 h in P. malariae.

4. Asexual parasitaemia. The presence in host red blood cells of asexual parasites. The level of

asexual parasitaemia can be expressed in several different ways: the percentage of infected

red blood cells, the number of infected cells per unit volume of blood, the number of

parasites seen in one microscopic field in a high-power examination of a thick blood film, or

the number of parasites seen per 200–1000 white blood cells in a high-power examination of

a thick blood film.

5. Cerebral malaria. Severe falciparum malaria with coma (Glasgow coma scale <11, Blantyre

coma scale <3). Malaria with coma persisting for >30 min after a seizure is considered to be

cerebral malaria.

6. Combination treatment (CT). A combination of two or more different classes of anti-

malarial medicines with unrelated mechanisms of action.

7. Cure. Elimination of the symptoms and asexual blood stages of the malaria parasite that

caused the patient or carer to seek treatment.

8. Drug resistance. Reduced susceptibility of the causal agent to a drug. WHO defines

resistance to anti-malarials as the ability of a parasite strain to survive and/ or multiply

despite the administration and absorption of a medicine given in doses equal to – or higher

than – those usually recommended but within the tolerance of the subject, with the caveat
 that the form of the drug active against the parasite must be able to gain access to the parasite

or the infected red blood cell for the duration of the time necessary for its normal action.

Resistance to anti-malarials arises because of the selection of parasites with genetic

mutations or gene amplifications that confer reduced susceptibility.

9. Gametocytes. Sexual stages of malaria parasites present in the host red blood cells, which

are infective to the anopheline mosquito.

10. Hypnozoites. Persistent liver stages of P. vivax and P. ovale malaria that remain dormant in

host hepatocytes for a fixed interval (3–45 weeks) before maturing to hepatic schizonts.

These then burst and release merozoites, which infect red blood cells. Hypnozoites are the

source of relapses.

11. Malaria pigment (haemozoin). A dark brown granular pigment formed by malaria parasites

as a by-product of haemoglobin catabolism. The pigment is evident in mature trophozoites

and schizonts.

12. Merozoites. Parasites released into the host bloodstream when a hepatic or erythrocytic

schizont bursts. These then invade the red blood cells.

13. Monotherapy. Anti-malarial treatment with a single medicine (either a single active

compound or a synergistic combination of two compounds with related mechanism of

action).

14. Plasmodium. A genus of protozoan vertebrate blood parasites that includes the causal agents

of malaria. Plasmodium falciparum, P. malariae, P. ovale and P. vivax cause malaria in

humans.

15. Pre-erythrocytic development. The life-cycle of the malaria parasite when it first enters the

host. Following inoculation into a human by the female anopheline mosquito, sporozoites

invade parenchyma cells in the host liver and multiply within the hepatocytes for 5–12 days,

forming hepatic schizonts. These then burst liberating merozoites into the bloodstream,

which subsequently invade red blood cells.

16. Radical cure. In P. vivax and P. ovale infections only, this comprises cure as defined above

plus prevention of relapses.

17. Rapid diagnostic test (RDT). An antigen-based stick, cassette or card test for malaria in

which a coloured line indicates that plasmodial antigens have been detected.

18. Recrudescence. The recurrence of asexual parasitaemia after treatment of the infection with

the same infection that caused the original illness (in endemic areas now defined by

molecular genotyping). This results from incomplete clearance of parasitaemia by treatment

and is therefore different to a relapse in P. vivax and P. ovale infections.

19. Recurrence. The recurrence of asexual parasitaemia following treatment. This can be caused

by a recrudescence, a relapse (in P. vivax and P. ovale infections only) or a new infection.

20. Relapse. The recurrence of asexual parasitaemia in P. vivax and P. ovale malaria deriving

from persisting liver stages. Relapse occurs when the blood stage infection has been

eliminated but hypnozoites persist in the liver and mature to form hepatic schizonts. After a

variable interval of weeks (tropical strains) or months (temperate strains) the hepatic

schizonts burst and liberate merozoites into the bloodstream.

21. Ring stage. Young usually ring-shaped intra-erythrocytic malaria parasites, before malaria

pigment is evident under microscopy.

22. Schizonts. Mature malaria parasites in host liver cells (hepatic schizonts) or red blood cells

(erythrocytic schizonts) that are undergoing nuclear division. This process is called

schizogony.

23. Selection pressure. Resistance to anti-malarials emerges and spreads because of the

selective survival advantage which resistant parasites have in the presence of anti-malarials

to which they are resistant. Selection pressure describes the intensity and magnitude of the

selection process; the greater the proportion of parasites in a given parasite population

exposed to concentrations of an anti-malarial that allow proliferation of resistant, but not

sensitive parasites, the greater is the selection pressure.

24. Severe anaemia. Haemoglobin concentration of <5 g/ 100 ml.

25. Severe falciparum malaria. Acute falciparum malaria with signs of severity and/ or

evidence of vital organ dysfunction.

26. Sporozoites. Motile malaria parasites that are infective to humans, inoculated by a feeding

female anopheline mosquito. The sporozoites invade hepatocytes.

27. Transmission intensity. The intensity of malaria transmission measured by the frequency

with which people living in an area are bitten by anopheline mosquitoes carrying sporozoites.

This is often expressed as the annual entomological inoculation rate (EIR), which is the

number of inoculations of malaria parasites received by one person in one year.

28. Trophozoites. Stage of development of the malaria parasites within host red blood cells from

the ring stage and before nuclear division. Mature trophozoites contain visible malaria

pigment.

29. Uncomplicated malaria. Symptomatic infection with malaria parasitaemia without signs of

severity and/ or evidence of vital organ dysfunction.

1. The scientist who first discovered the malaria germ in the blood of malaria
patients was
(a) Charles Alphonse Laveran
(b) Ronald Ross
(c) Edward Jener
(d) Charles Darwin
(e) Isaac Newton

2. The therapeutically active bark of cinchoma tree contains the following

ingredients except
(a) Chloroquine
(b) Quinine
(c) Quinidine
(d) Chinchonine
(e) Cinchonidine

3. Malaria is a worldwide disease; the number of people exposed to it is estimated to

be about
(a) 2.2 billion
(b) 200 million
(c) 1 billion
(d) 400 million
(e) 5 billion
4. The four important pathologic processes identified with malaria include the
following except
(a) Fever
(b) Anaemia
(c) Immunopathologic events
(d) Tissue Anoxia
(e) Auto haemolysis

5. Cerebral malaria is compatible with severe falciparium malaria with

(a) Glasgow coma scale < 11
(b) Blantyre coma scale < 4
(c) Malaria with coma persisting > 20 min after a seizure
(d) Cocacola urine
(e) Nystagmus.

Answers

1 a
2 a
3 a
4 e
5 a

Professor O. A. Oyelami,

WACP revision Course, August 2008.